Pharm 101: Acetazolamide

Classes

Carbonic Anhydrase Inhibitor (CAI)


Pharmacodynamics
  • Carbonic anhydrase enzyme is predominantly located in epithelial cells of PCT and catalyses:
    • Dehydration of H2CO3 to CO2 at luminal membrane
    • Subsequent rehydration of CO2 to H2CO3 in cytoplasm of PCT cells
  • H2CO3 is converted to H and HCO3 in the cytoplasm, and HCO3 reabsorbed on the interstitial membrane with Na, and H secreted via Na/K transporter on the luminal membrane
  • By blocking this enzyme, CAIs blunt NaHCO3 reabsorption and cause diuresis
  • They also reduce renal secretion of H in the PCT

Pharmacokinetics
  • Well absorbed orally
  • An increase in urine pH from HCO3 diuresis occurs within 30 minutes, is maximal at 2 hours, and persists for 12 hours after a single dose
  • Excretion by secretion in PCT, therefore dosing must be reduced in renal failure

Clinical uses
  • Glaucoma
    • Reduce aqueous humour formation, decreasing intraocular pressure
  • Urinary alkalinisation
  • Metabolic alkalosis due to excessive diuretic use in heart failure, when replacement of intravascular volume contraindicated
  • Acute mountain sickness
    • Decreases CSF formation and pH, which diminishes symptoms of cerebral oedema and increases ventilation

Adverse effects
  • Hyperchloraemic metabolic acidosis
    • Due to chronic reduction of HCO3 stores
    • Limits diuretic efficacy of these drugs to 2-3 days
  • Renal calculi
    • Increased urinary calcium and phosphate occur during bicarbonaturic response, and these are relatively insoluble at alkaline pH
  • Renal K wasting
    • Increased Na (along with HCO3) delivery to the collecting tubule, which creates a lumen-negative electrical potential enhancing K secretion
  • Drowsiness and paraesthesiae

Precautions/contraindications
  • Renal failure: neurological toxicity
  • Hepatic failure:
    • Urinary alkalinisation of urine reduced urinary excretion of NH4, by converting it to rapidly absorbed NH3
    • Leads to hyperammonemia and hepatic encephalopathy in predisposed patients with cirrhosis

Further reading

References
  • Katzung BG. Basic & Clinical Pharmacology. 14th ed. United States of America: McGraw-Hill Education; 2018. 259-261, 272 p.

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MBBS (UWA) CCPU (RCE, Biliary, DVT, E-FAST, AAA) Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

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